Background and objective: To assess the influence of hepatitis C virus (HCV) co-infection and the extent of liver fibrosis on lopinavir/ritonavir pharmacokinetics in HIV-infected patients without liver function impairment. Methods: Cross-sectional, comparative study enrolling HIV-infected adults receiving lopinavir/ritonavir (400mg/100mg twice daily). HIV/HCV co-infected patients were grouped as having advanced fibrosis (HCV+/FIB+, n = 7) or not (HCV+/FIB-, n = 8) based on the FIB-4 index. A full concentration-time profile was obtained for each patient, and blood samples were collected before (0), and 1, 2, 4, 6, 8, 10 and 12 hours after a lopinavir/ritonavir dose. Lopinavir and ritonavir concentrations in plasma were determined by high-performance liquid chromatography. Maximum and minimum plasma concentrations (Cmax and Cmin), area under the plasma concentration-time curve from 0 to 12 hours (AUC12), apparent oral clearance at steady state (CLss/F), and apparent volume of distribution after oral administration (Vd/F) were calculated for each individual using a non-compartmental approach. Results: Twenty-six HCV- and 22 HCV+ patients were enrolled. Lopinavir and ritonavir pharmacokinetics were comparable between HCV- and HCV+ patients. However, the Vd/F of lopinavir was 125% higher in HCV+/FIB+ patients than in HCV- patients (p = 0.015) and 107% higher than in HCV+/FIB- (p = 0.040) patients. The CLss/F of ritonavir was 40% lower in HCV+/FIB+ patients than in HCV- patients (p = 0.005) and 44% lower than in HCV+/FIB- patients (p = 0.040). Thus, for ritonavir AUC12, Cmax and Cmin in HCV+/FIB+ patients were 63%, 86% and 100% higher, respectively, when compared with those parameters in HCV- patients (p = 0.005, p = 0.012 and p = 0.015, respectively), and 80%, 86% and 100% higher, respectively, when compared with levels in HCV+/FIB-patients (p = 0.040, p = 0.040 and p = 0.029, respectively). Conclusion: Lopinavir exposure is similar in HIV-infected patients with or without HCV co-infection and without liver function impairment. However, ritonavir exposure may be higher in this setting, particularly in individuals with advanced liver fibrosis. © 2007 Adis Data Information BV. All rights reserved.